期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 4, 页码 E610-E619出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1715911114
关键词
neural stem cells; cellular dynamics; modeling; single; cell sequencing; ki67
资金
- NIRM/Clevers and Stichting Vrienden van het Hubrecht
- NIH/MIT [5710002735]
- Stichting Vrienden van het Hubrecht
- European Research Council [ERC-AdG 294325-GeneNoiseControl]
- Wellcome Trust [098357/Z/12/Z]
- [EU/232814-StemCellMark]
- [Skolkovo 077 MPA]
- [KWF/PF-HUBR 2007-3956]
The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67(iresCreER) allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.
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